Mucin-1 (Mucin1, also described as MUC1 hereinafter), which is one kind of mucin, is a tumor-associated antigen; MUC1 is a high molecular weight glycoprotein which is expressed by many adenocarcinomas. It is known that MUC1 is a membrane bound protein with an extracellular domain essential for the function of said protein; the extracellular domain of MUC1 is mainly composed of 30 to 90 tandem-type repeats of a core sequence of 20 amino acids (also referred to as “Tn20-mer” hereinafter in the present description; HGVTSAPDTRPAPGSTAPPA (SEQ ID No.: 1)) rich in serine, threonine and proline. The repetition number of the Tn20-mer expressed is genetically determined by an individual, resulting in size polymorphisms.
It is believed that all minimum sequence recognitions of most MUC1-reactive monoclonal antibodies are present in APDTRPAP, and belong to a “type 1β-turn”. The sequence SAPDTRP in the MUC1 tandem-type repeat is an immunodominant B cell epitope, and a T cell epitope of the tandem-type repeat is located at the pentamer PDTRP.
Tumor MUC1 generally has low glycosylation, and a glycosylation site frequently has abnormal sugar chain extension. This abnormal glycosylation generates the result of exposure to a normal cryptic peptide epitope and the creation of a novel carbohydrate epitope. Due to their high molecular weight (2×105 to 5×107 daltons) and extensive glycosylation, a cellular membrane mucin is present as a soft rod, and protrudes from a cellular surface at a relatively large distance. Therefore, the mucin forms important components of a polysaccharide coat, and is probably a first point of cellular contact between an antibody and an immune system.
In addition, Patent Document 1 describes the anti-MUC1 antibody DF3-P. This DF3-P reacts with MUC1 without sugar chains, and thus sugar chain specificity is not apparent.
Patent Document 2 describes the anti-MUC1 antibodies 7F11 and 1E4. 7F11 and 1E4 bind to glycosylated MUC1, but sugar chain specificity is not apparent.
Patent Document 3 describes the anti-MUC1 antibody Alt-1. Alt-1 binds to MUC1 independently of a sugar chain, and sugar chain specificity is not apparent.
Non-Patent Document 1 describes the anti-MUC1 antibodies Panko1 and Panko2. In the anti-MUC1 antibodies Panko1 and Panko2, when a tandem repeat is short, binding is weak. Sugar specificity of the anti-MUC1 antibodies Panko1 and Panko2 is not apparent.
Non-Patent Document 2 discloses the anti-MUC1 antibody VU-2G7 which was made by a procedure similar to that of Non-Patent Document 1 in that a glycopeptide is used as an immunogen. It is described that the antibody has the ability to recognize sugar chain specificity.
It also cannot be said that, in the Panko monoclonal antibody disclosed in Patent Document 4, selectivity is sufficient and, therefore, a novel therapeutic composition which selectively binds to tumor-associated MUC1, and can reduce, reverse or prevent its influence in cancers is still required. Therefore, a therapeutic composition comprising a binder which can bind to an epitope of MUC1, in particular, comprising both a peptide and a tumor-specific carbohydrate is required.